Department of Orthopaedic Surgery, Kochi University, Oko-cho Kohasu, Nankoku 783-8505, Japan.
J Biomed Sci. 2012 Aug 21;19(1):77. doi: 10.1186/1423-0127-19-77.
Recent data have suggested a relationship between acute arthritic pain and acid sensing ion channel 3 (ASIC3) on primary afferent fibers innervating joints. The purpose of this study was to clarify the role of ASIC3 in a rat model of osteoarthritis (OA) which is considered a degenerative rather than an inflammatory disease.
We induced OA via intra-articular mono-iodoacetate (MIA) injection, and evaluated pain-related behaviors including weight bearing measured with an incapacitance tester and paw withdrawal threshold in a von Frey hair test, histology of affected knee joint, and immunohistochemistry of knee joint afferents. We also assessed the effect of ASIC3 selective peptide blocker (APETx2) on pain behavior, disease progression, and ASIC3 expression in knee joint afferents.
OA rats showed not only weight-bearing pain but also mechanical hyperalgesia outside the knee joint (secondary hyperalgesia). ASIC3 expression in knee joint afferents was significantly upregulated approximately twofold at Day 14. Continuous intra-articular injections of APETx2 inhibited weight distribution asymmetry and secondary hyperalgesia by attenuating ASIC3 upregulation in knee joint afferents. Histology of ipsilateral knee joint showed APETx2 worked chondroprotectively if administered in the early, but not late phase.
Local ASIC3 immunoreactive nerve is strongly associated with weight-bearing pain and secondary hyperalgesia in MIA-induced OA model. APETx2 inhibited ASIC3 upregulation in knee joint afferents regardless of the time-point of administration. Furthermore, early administration of APETx2 prevented cartilage damage. APETx2 is a novel, promising drug for OA by relieving pain and inhibiting disease progression.
最近的数据表明，急性关节炎疼痛与支配关节的初级传入纤维中的酸感应离子通道 3（ASIC3）之间存在关系。本研究的目的是阐明 ASIC3 在骨关节炎（OA）大鼠模型中的作用，OA 被认为是一种退行性疾病而不是炎症性疾病。
我们通过关节内单碘乙酸（MIA）注射诱导 OA，并通过容量测定仪评估与疼痛相关的行为，包括承重，以及在 von Frey 毛发试验中评估爪撤回阈值，受影响的膝关节组织学和膝关节传入神经的免疫组织化学。我们还评估了 ASIC3 选择性肽阻滞剂（APETx2）对疼痛行为、疾病进展和膝关节传入神经中 ASIC3 表达的影响。
OA 大鼠不仅表现出承重疼痛，而且还表现出膝关节外的机械性痛觉过敏（继发性痛觉过敏）。膝关节传入神经中 ASIC3 的表达在第 14 天左右显著上调约两倍。持续的关节内注射 APETx2 通过减轻膝关节传入神经中 ASIC3 的上调来抑制体重分布不对称和继发性痛觉过敏。同侧膝关节组织学显示，如果在早期而不是晚期给予 APETx2，则具有软骨保护作用。
局部 ASIC3 免疫反应性神经与 MIA 诱导的 OA 模型中的承重疼痛和继发性痛觉过敏密切相关。APETx2 抑制了膝关节传入神经中 ASIC3 的上调，无论给药时间点如何。此外，APETx2 的早期给药可防止软骨损伤。APETx2 通过缓解疼痛和抑制疾病进展，是一种治疗 OA 的新型有前途的药物。
